A major cell surface glycoprotein (CSP) that is involved in cellular adhesions is adapted after malignant transformation of fibroblasts in vitro. Reconstitution of purified, exogenous CSP on the surfaces of transformed cells partially restores a normal phenotype, including a fibroblastic cell morphology and alignment of cells, a smooth cell surface architecture with few microvilli and ruffles, and a restoration of intracellular microfilament bundles. CSP does not decrease the rate of glucose or amino acid transport. The decrease in CSP after transformation is due primarily to decreased biosynthesis, although losses from increased rates of protein turnover also contribute. The decreased biosynthesis appears to result from decreased amounts of messenger RNA for CSP. Our objectives will be to determine the composition and structure of CSP, and the mechanisms by which it helps to maintain normal cell behavior. BIBLIOGRAPHIC REFERENCES: Yamada, K.M., Ohanian, S.H., and Pastan, I.: Cell Surface Protein Decreases Microvilli and Ruffles on Transformed Mouse and Chick Cells. Cell 9: 241-245, 1976. Yamada, K.M., and Pastan, I.: The Relationship between Cell Surface Protein and Glucose and alpha-Aminoisobutyrate Transport in Transformed Chick and Mouse Cells. J. Cell. Physiol. 98: 827-230, 1976.